Project 4 aims to explore age-related neurodegeneration from the perspective of one particular neuronal[unreadable] population, namely the locus coeruleus noradrenergic (LC-NE) neurons. This neuronal population[unreadable] deteriorates in the brain during normal aging but also in the brain of Alzheimer's and Parkinson's disease[unreadable] patients. The activity of LC-NE neurons may act as an endogenous protection against insults such as[unreadable] neuroinflammation and oxidative stress. Therefore this project aims to study the role of locus coeruleus in[unreadable] maintaining the overall health of the limbic system and the nigrostriatal system during aging. Since intrinsic[unreadable] vs. extrinsic factors influencing neurodegeneration are difficult to delineate in the intact animal, we propose[unreadable] to utilize intraocular transplants consisting of LC-NE neurons in combination with hippocampal and midbrain[unreadable] nigra dopamine neurons, to examine the specific function of these neurons in aging and age-related[unreadable] neurodegeneration. Intrinsic vs. extrinsic factors will also be examined with blueberry diets (BB) in[unreadable] collaboration with Project 1, to explore the mechanism for its neuroprotective properties. We propose the[unreadable] following two hypotheses for Project 4: 1) LC-NE neurons play a role in protecting other brain regions from[unreadable] oxidative stress and/or inflammation, and age-related degeneration of these neurons leads to secondary[unreadable] damage in the hippocampus, and the midbrain nigra region. 2) Treatment with blueberry extract can reverse[unreadable] age-related degeneration of the LC-NE system, and improve graft survival into the aged host.[unreadable] Based on these hypotheses, we have formulated three aims in which we will explore the relationship[unreadable] between LC-NE innervation and age-related inflammatory and oxidative stress markers. Project 4 will[unreadable] collaborate with Project 1 in terms of blueberry studies, with Project 2 in terms of microglial markers, with[unreadable] Project 3 in terms of the M1/M2 specific markers, and with Project 5 in terms of comparison of protein levels[unreadable] with mRNA expression for critical markers of neurodegeneration with aging.[unreadable]